Biomedical subjects

D Sheppard

Publications and source records attributed to D Sheppard.

At least 145 records · Page 8Linked to original sources

PubMed1984

Respiratory water loss as a stimulus to exercise-induced bronchoconstriction.

Exercise and the resultant hyperpnea increase the magnitude of many stimuli delivered to the airways. Thus clinical "exercise-induced" bronchoconstriction can probably be initiated by a number of stimuli including, for example, sulfur dioxide, which is present in polluted air. In the laboratory, when subjects perform exercise breathing clean air, the water content of the inspired air is a major determinant of the bronchoconstriction induced, whereas in our hands, the temperature of the inspired air is of little or no importance, even over a range associated with significant differences in airway cooling. These observations support the view that water loss is an important stimulus to exercise-induced bronchoconstriction, perhaps as a result of a transient increase in the osmolarity of airway surface liquid.

Asthma↗

PubMed1984

Variable inhibition of histamine-induced bronchoconstriction by atropine in subjects with asthma.

To determine whether treatment with atropine causes dose-dependent inhibition of histamine-induced bronchoconstriction, we constructed dose-response curves to inhaled histamine after inhalation of placebo and 0.26 and 2.08 mg of atropine in eight subjects with mild asthma. Both doses of atropine significantly inhibited histamine-induced bronchoconstriction, and 2.08 mg caused significantly greater inhibition than 0.26 mg. Baseline specific airway resistance was significantly reduced by both doses of atropine but was no different after 2.08 mg than after 0.26 mg. There were considerable differences in the efficacy of atropine among individuals. We conclude that atropine causes dose-dependent inhibition of histamine-induced bronchoconstriction and that this effect is not merely a function of the atropine-induced in baseline airway caliber. The large magnitude of the atropine effect in some subjects and the small magnitude of the effect in others suggest that there is variability in the degree of involvement of muscarinic mechanisms in the exaggerated bronchomotor response to histamine in asthmatic subjects.

Adult↗

PubMed1984

Interaction of sulfur dioxide and dry cold air in causing bronchoconstriction in asthmatic subjects.

To determine whether sulfur dioxide and airway cooling and drying interact in causing bronchoconstriction in persons who have asthma, we measured specific airway resistance in seven asthmatic subjects before and after they performed voluntary eucapnic hyperpnea for 3 min breathing four different gas mixtures. The mixtures, which the subjects breathed through a mouthpiece in random order on 4 different days, were 1) humidified room-temperature air, 2) humidified room-temperature air containing 0.5 ppm SO2, 3) cold dry air, and 4) cold dry air containing 0.5 ppm SO2. Each subject breathed at a rate and depth known from preliminary studies to cause little or no bronchoconstriction when that subject inhaled 0.5 ppm SO2 in humidified room-temperature air or cold dry air. When given independently in the blinded study, 0.5 ppm SO2 or cold dry air again caused insignificant bronchoconstriction, but when given together the two stimuli caused significant bronchoconstriction, as indicated by an increase in specific airway resistance from 6.94 +/- 2.85 to 22.35 +/- 10.28 l X cmH2O X l-1 X s (mean +/- SD) (P less than 0.001). thus airway cooling and/or drying increases the bronchoconstriction induced by inhaled SO2 in persons who have asthma. This increase suggests that persons who have asthma may be more sensitive to the bronchoconstrictor effects of ambient SO2 in cold dry environments than in warm moist environments.

Adult↗

PubMed1984

Magnitude of the interaction between the bronchomotor effects of sulfur dioxide and those of dry (cold) air.

We studied the interaction between airway drying (cooling) and inhalation of sulfur dioxide (SO2) causing bronchoconstriction in 8 subjects with mild asthma. On 3 separate days, we measured specific airway resistance (SRaw) before and after the subject performed voluntary eucapnic hyperpnea at a constant minute ventilation (30 to 40 L/min) for successive 3-min periods with doubling concentrations of SO2 in dry cold air (-20 degrees C, 0% relative humidity), in dry warm air (22 degrees C, 0% relative humidity), and in partially humidified warm air (22 degrees C, 70% relative humidity). On another day, we measured SRaw before and after the subject performed each of 6 successive 3-min periods of voluntary eucapnic hyperpnea at the same minute ventilation breathing dry cold air without SO2. The concentration of SO2 that caused a 100% increase in SRaw was significantly lower in dry cold air and in dry warm air than it was in humidified warm air. Repeated hyperpnea with dry cold air without SO2 at the same ventilation had no effect on SRaw. We then had the same subjects perform voluntary eucapnic hyperpnea at successively increasing levels of ventilation on 3 different days with dry air alone, dry air with 0.1 ppm SO2, or dry air with 0.25 ppm SO2. The minute ventilation that caused an 80% increase in SRaw was significantly lower for hyperpnea with 0.1 and with 0.25 ppm SO2 than for dry air without SO2, but these differences were small.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Morphine sulfate inhibits bronchoconstriction in subjects with mild asthma whose responses are inhibited by atropine.

To determine whether morphine sulfate alters the bronchoconstrictive response to inhalation of distilled water, we gave 13 subjects with mild asthma 0.15 mg/kg morphine sulfate or normal saline intravenously, after which they inhaled increasing volumes of nebulized distilled water from an ultrasonic nebulizer. We constructed stimulus-response curves, and by interpolation determined the provocative output of the nebulizer that resulted in a 50% increase in SRaw from baseline (PO50). On a separate day the subjects inhaled 2.0 mg of atropine sulfate 30 min before they inhaled distilled water. We compared the bronchoconstrictive response after morphine and after atropine with the bronchoconstrictive response after saline by determining the ratio of the PO50 values. Atropine was considered effective in inhibiting bronchoconstriction in 7 of the 13 subjects in whom the ratio of PO50 after atropine to the PO50 after saline was greater than 2.0. By similar criteria, morphine was also considered effective in 5 of these 7 subjects. Neither atropine nor morphine was effective in the remaining 6 subjects. By chi-square analysis, we found a positive correlation between the inhibitory effects of morphine and those of atropine (p less than 0.05). In the 5 subjects in whom morphine was effective, naloxone reversed the inhibitory effect of morphine. Atropine caused significant baseline bronchodilation when compared with placebo (normal saline), whereas morphine did not. We conclude that opiate receptor stimulation by morphine causes inhibition of the vagally mediated component of water-induced bronchoconstriction.

Adult↗

PubMed1984

Alteration in osmolarity of inhaled aerosols cause bronchoconstriction and cough, but absence of a permeant anion causes cough alone.

To determine whether cough and bronchoconstriction result from alterations in the osmolarity or alterations in the ion concentration of inhaled aerosols and to determine if the specific ions in the aerosol are important, we had 9 subjects with mild asthma inhale various solutions while we recorded cough and measured specific airway resistance. To evaluate the effects of altering osmolarity and ion concentration separately, we administered aerosols of hypo-osmolar distilled water (0 mosm), iso-osmolar sodium chloride (308 mosm), iso-osmolar dextrose in water (308 mosm), hyperosmolar sodium chloride (1,232 mosm), and a hyperosmolar solution of dextrose and sodium chloride (1,232 mosm). To evaluate cough without bronchoconstriction, we had the subjects inhale metaproterenol before inhaling the same aerosols. To determine whether the absence of a specific ion was important in causing cough or bronchoconstriction, we had the subjects inhale iso-osmolar solutions of sodium bromide, sodium gluconate, and lysine monohydrochloride. We found that alteration in osmolarity away from iso-osmolarity of inhaled aerosols is a stimulus for bronchoconstriction in subjects with mild asthma. Absence of ions in the presence of iso-osmolarity is not a stimulus for bronchoconstriction, but the absence of a permeant anion is a stimulus for cough. Thus, we found that the responses of cough and bronchoconstriction to inhaled aerosols can be separated.

Adult↗

PubMed1983

Tolerance to sulfur dioxide-induced bronchoconstriction in subjects with asthma.

A study to determine whether the bronchoconstriction induced by low concentration of sulfur dioxide in subjects with asthma decreases with repeated exposure was undertaken. Eight subjects with asthma performed 3 min of voluntary eucapnic hyperpnea with 0.5 ppm of SO2 in humidified filtered air three times at 30-min intervals and we measured specific airway resistance (SRaw) before and after each period of hyperpnea. Specific airway resistance increased significantly more after the first exposure to SO2 [(from 7.6 +/- 1.7 to 15.5 +/- 2.0 L x cm H2O/liter/sec (mean +/- SEM)] than after the second (from 8.1 +/- 1.3 to 10.8 +/- 1.6) or third (from 7.6 +/- 1.6 to 10.1 +/- 1.9) exposures (P less than 0.025). When seven subjects repeated hyperpnea with SO2 24 hr and 7 days later, SRaw increased as much as it had after the first exposure (from 8.2 +/- 2.5 to 15.5 +/- 4.5 at 24 hr and from 6.6 +/- 1.4 to 15.4 +/- 2.1 at 7 days). In four subjects repeated exposure to SO2 caused short-term inhibition of the bronchomotor response to SO2 but did not inhibit the bronchomotor response to histamine aerosol. It was concluded that repeated exposures to a low concentration of SO2 over a short period (on 1 day) can induce tolerance to the bronchomotor effects of SO2 in subjects with asthma. Tolerance to the bronchomotor effects of SO2 is not caused by decreased responsiveness of airway smooth muscle or a generalized decrease in the responsiveness of vagal reflex pathways since the bronchomotor response to histamine is preserved.

Adult↗

PubMed1983

Effect of route of atropine delivery on bronchospasm from cold air and methacholine.

We undertook a study to determine whether the apparent disparity between the dose of inhaled atropine required to inhibit the bronchoconstriction induced by inhaled methacholine and the dose required to inhibit the bronchoconstriction induced by eucapnic hyperpnea with cold air is a function of the route of administration of atropine. In six subjects with asthma, we constructed dose-response curves to inhaled methacholine and to eucapnic hyperpnea with cold air after treatment with inhaled atropine (0.5 mg delivered) and intravenous placebo, with inhaled placebo and intravenous atropine (0.5 mg injected), and with inhaled and intravenous placebos. Atropine by either route shifted the dose-response curves to both cold air and to methacholine to the right. In every subject, however, inhaled atropine caused a markedly greater rightward shift of the inhaled methacholine dose-response curve than did intravenous atropine, whereas inhaled and intravenous atropine had similar effects on the cold air dose-response curve. These findings suggest that the apparent disparity between the doses of atropine required to inhibit methacholine- and cold air-induced bronchoconstriction may be a function of the route of administration of atropine and thus does not imply a nonmuscarinic action of atropine. The findings support the view that cold air causes bronchoconstriction via muscarinic pathways.

Adult↗

PubMed1983

Intravenous versus inhaled atropine for inhibiting bronchoconstrictor responses in dogs.

We studied whether the muscarinic antagonist, atropine, given intravenously or by inhalation, inhibits the bronchoconstrictor responses to inhaled acetylcholine and to acetylcholine released by electrical stimulation of the vagus nerves to the same degree. We assessed bronchoconstrictor responses in anesthetized dogs by determining the increase in total pulmonary resistance before and after increasing doses of atropine and then constructing inhibition dose-response curves. Before atropine the responses to the two stimuli were equal in magnitude. After intravenous atropine (initial dose 0.12 micrograms/kg, total dose 16 micrograms/kg) both responses were progressively inhibited to a similar degree. By contrast, after inhaled atropine (initial dose 0.02 micrograms/kg, total dose 2.4 micrograms/kg) the response to acetylcholine inhalation was inhibited to a much greater degree than the response to vagal stimulation. Thus, in studies designed to inhibit bronchoconstriction due to an inhaled muscarinic agonist to the same degree as bronchoconstriction due to a vagal reflex, atropine might better be given intravenously than by inhalation.

Aerosols↗

PubMed1983

Mechanism of cough and bronchoconstriction induced by distilled water aerosol.

We studied the relationship between cough and bronchoconstriction caused by inhaled distilled water aerosol in 8 subjects with asthma by measuring specific airways resistance (SRaw) and recording cough while subjects breathed serially increasing volumes of distilled water or normal saline aerosol produced by an ultrasonic nebulizer. We performed the distilled water dose-response curves after no treatment and after treatment with cromolyn aerosol, lidocaine aerosol, or atropine aerosol in doses of 0.2 mg and 2.0 mg on separate days. Without prior treatment, distilled water aerosol caused cough in 7 of 8 subjects and a marked increase in SRaw in every subject, whereas saline aerosol did not cause cough or a greater than 50% increase in SRaw in any subject. The 2 doses of atropine caused an equivalent reduction in baseline SRaw, but 2.0 mg caused greater inhibition of water-induced bronchoconstriction than did 0.2 mg. Neither dose of atropine inhibited cough. These data suggest that water-induced bronchoconstriction involves cholinergic nerves and that water-induced cough is not dependent on bronchoconstriction. Lidocaine inhibited cough but not bronchoconstriction, whereas cromolyn inhibited bronchoconstriction but not cough, suggesting that cromolyn does not inhibit bronchoconstriction by a generalized inhibition of airway afferent nerves.

Adolescent↗

PubMed1983

Effect of exercise rate and route of inhalation on sulfur-dioxide-induced bronchoconstriction in asthmatic subjects.

Nine asthmatic subjects exercised at low, moderate, and high work rates on a cycle ergometer while breathing filtered, humidified air with or without 0.5 ppm of sulfur dioxide (SO2) in a double-blind study. Subjects first performed these experiments breathing through a mouthpiece while wearing a noseclip (oral breathing) and then repeated the experiments breathing through a facemask that separated and permitted independent measurement of oral and nasal air flow (oronasal breathing). We determined specific airway resistance before and after exercise by body plethysmography. Inhaled by mouthpiece, 0.5 ppm So2 caused bronchoconstriction at moderate and high but not at low work rates. There was a dose-response relationship between the work rate performed and the degree of bronchoconstriction induced. Inhaled oronasally, 0.5 ppm SO2 caused bronchoconstriction only at the high work rate. These findings demonstrate that So2-induced bronchoconstriction is dependent on the work rate of exercise during exposure, that oronasal breathing is only partially effective in preventing the bronchoconstriction observed with oral breathing, and that oronasal breathing is less effective in preventing bronchoconstriction with high than with moderate exercise at this concentration of SO2.

Adult↗

PubMed1983

Antihistaminic versus anticholinergic effects of atropine on canine trachealis muscle.

To determine antihistaminic versus anticholinergic effects of atropine in airway smooth muscle, we used an in vitro preparation of canine trachealis muscle strips and determined atropine's effect on contractile responses induced by histamine or by electrical field stimulation of cholinergic nerves. In the first series of experiments, 53 strips had initial responses to field stimulation determined and were then randomly assigned to a control group or to a group treated with atropine before field stimulation was repeated and histamine was given. Atropine in concentrations of 10(-8), 10(-7), and 10(-6) M decreased the response to field stimulation to 61.4, 10.5, and 0% of the initial response, respectively, but had no effect on the responses to histamine. In the second series of experiments, 24 strips were treated with indomethacin to prevent histamine tachyphylaxis; these strips had initial responses to both field stimulation and histamine determined and were then assigned to a control group or to a group treated with atropine before field stimulation and histamine were repeated. In these experiments, a concentration of atropine (10(-6) M), which again completely blocked the response to field stimulation, still had no effect on histamine-induced contraction. We conclude that atropine in a concentration that completely blocks the response to cholinergic nerve stimulation has no antihistaminic effect.

Animals↗

PubMed1983

Sulfur dioxide-induced bronchoconstriction in freely breathing, exercising, asthmatic subjects.

The purpose of this study was to determine whether 0.50 ppm sulfur dioxide (SO2) in filtered air causes bronchoconstriction in freely breathing asthmatic subjects exercising at a moderately heavy work rate. Ten volunteers who had mild asthma breathed air containing no SO2 or containing 0.50 ppm SO2 In an exposure chamber as they exercised for 5 min on a cycle ergometer at a work rate of 750 kilopond meters/min (about 125 watts). We determined their specific airway resistance by body plethysmography before and after exercise. Specific airway resistance increased by 13.55 +/- 9.18 cm H2O X s (mean +/- SD) when subjects exercised and breathed 0.50 ppm SO2 but only by 2.24 +/- 2.34 when they exercised and breathed air without SO2 (p less than 0.005). Thus, 0.50 ppm SO2 causes significant bronchoconstriction in freely breathing asthmatics during moderately heavy exercise.

Adult↗

PubMed1983

Chest pain and hypoxemia from inhalation of a trichloroethane aerosol product.

A 25-year-old man developed severe shortness of breath, constricting chest pressure, chest pain, cough and myalgia following acute exposure to a waterproofing aerosol that contained trichloroethane. He became febrile and developed a small area of atetectasis with significant hypoxemia. Recovery was complete within 36 hours. This experience suggests that casual use of a trichloroethane aerosol with a surface active agent can cause acute pulmonary toxicity. The mechanism of this injury is unknown.

Adult↗

PubMed1982

The effect of neurotensin on food consumption in the rat.

The effect of neurotensin on feeding behavior were studied in rats. Intracerebroventricular administration of neurotensin (3.3-30 micrograms) produced a dose-related decrease in food intake in 24 h food deprived rats. Acute intracerebroventricular injection of neurotensin (30 micrograms) shortly after the ingestion of a novel flavor did not produce a flavor aversion during testing 48 h later, suggesting that reduction of food intake by low doses of centrally administered neurotensin is not related to a conditioned taste aversion. Intracerebroventricularly administered thyrotropin-releasing hormone (2.2 micrograms) also inhibited food intake and appeared to attenuate slightly the inhibition of food intake induced by 10 micrograms neurotensin.

Animals↗

PubMed1982

Dose-dependent inhibition of cold air-induced bronchoconstriction by atropine.

We undertook a study to demonstrate whether inhalation of atropine could inhibit cold air-induced bronchoconstriction in a dose-dependent fashion. In seven subjects with asthma we assessed the effects of placebo and of various doses of inhaled atropine (0.13-2.08 mg) on a base-line specific airway resistance (sRaw) and on the increase in sRaw produced by 5 min of voluntary eucapnic hyperventilation with subfreezing air at -17 degrees C. We also assessed the effect of the lowest doses of atropine on the increase in sRaw produced by five breaths of 1.0% metacholine. Atropine in doses of 0.13 or 0.26 mg caused a maximal reduction in base-line sRaw and completely inhibited the effect of 1.0% methacholine on sRaw, but it did not inhibit the bronchomotor response to cold air. Higher doses of atropine did inhibit the effect of cold air on sRaw in a dose-dependent fashion. The dose of atropine required to inhibit this effect of cold air varied with the increase in sRaw produced by cold air after placebo. These results suggest that cold air causes bronchoconstriction through vagal pathways and that higher doses of antimuscarinic agents are required to inhibit vagally mediated bronchoconstriction than those required to reduce base-line airway tone or to inhibit the effects of a large dose of an inhaled muscarinic agonist.

Adult↗

PubMed1982

Effect of the oronasal breathing route on sulfur dioxide-induced bronchoconstriction in exercising asthmatic subjects.

We undertook a study to determine how the oronasal breathing route affects the bronchoconstrictor response to sulfur dioxide (SO2) inhaled by asthmatic subjects during exercise. In 6 subjects, we compared the changes in specific airway resistance (SRaw) caused by breathing humidified air through a mouthpiece during 5 min of exercise on a bicycle ergometer (550 kpm/min) to the changes caused by breathing humidified air plus 0.5 ppm of SO2, (a) through a mouthpiece (oral breathing), (b) by facemask (oronasal breathing), and (c) by facemask with the mouth occluded (nasal breathing) during exercise. Breathing humidified air plus 0.5 ppm of SO2 through a mouthpiece or by facemask during exercise significantly increased SRaw in all 6 subjects, and breathing humidified air plus 0.5 PPM of SO2 by facemask with the mouth occluded significantly increased SRaw in 5 of 6 subjects. The increase in SRaw caused by breathing humidified air plus 0.5 PPM of SO2 through a mouthpiece was not significantly different from the increase caused by breathing SO2 by facemask (p greater than 0.05), but was significantly greater than the increase caused by breathing SO2 by facemask with the mouth occluded (p less than 0.05). These results indicate that although nasal breathing partially protected against SO2-induced bronchoconstriction in our subjects, both oral and oronasal breathing of low concentrations of SO2 during exercise can cause significant bronchoconstriction in people with asthma.

Adult↗

PubMed1982

Occupational asthma.

Bronchospasm is a common cause of morbidity in the workplace. More than 100 agents are now recognized as occupational causes of asthma and numerous agents can cause exacerbations of preexisting asthma. Because of the large number of potential causative agents and the complexity of modern industrial processes, knowledge of the characteristic clinical features of occupational asthma is the key to recognizing this disease. Early diagnosis of occupational asthma is important in preventing long-term morbidity. Present evidence that prolonged exposure to some work-encountered agents can cause asthma that persists for years after the end of exposure suggests that avoidance is the only acceptable countermeasure against this disease.

Air Pollutants↗